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There is a high risk of side effects when prescribing antidepressants in the elderly. These can
be avoided or minimised by tailoring the choice of antidepressant to the individual, by being
aware of potential drug interactions and by bearing in mind the impact of co-morbidities.
Drs Ayodeji Soyinka and David Lawley explore the evidence base and main side effects of
antidepressants in common use in the elderly and how these might influence prescribing.
62 Psychiatry
interactions and by bearing in mind the impact
of co-morbidities. In this article, we explore the
evidence base for effectiveness and the main
side effects of antidepressants in common use
in the elderly and how both these factors might
influence prescribing.
Effectiveness
The efficacy and effectiveness of antidepressant
treatment in depressed elderly people have
been demonstrated in randomised control trials
and reviews14,15. Available data suggest that
antidepressants are effective in 50 to 60 per cent
of cases compared with a 30 per cent recovery
rate on placebo4. The placebo response is greatest
in those with mild depressive disorder and hence
antidepressants are not recommended as initial
treatment in those with mild depressive disorders.
This is consistent with the NICE guideline9.
All antidepressants have roughly equal efficacy,
although the effectiveness may differ depending
on tolerability. The general consensus is that
SSRIs and other newer antidepressants are
better tolerated than the tricyclics and related
antidepressants. In line with this, NICE
recommends that an SSRI should be first choice
when an antidepressant is to be prescribed
in routine care9. Of course, the choice of
antidepressant will depend on other factors as well
as including patients preference, co-morbidity,
potential side effects, risk of drug interactions,
past use of antidepressants and risk of overdose as
well as associated symptoms of depression such as
insomnia and agitation.
In patients severely ill with depression there
is a contention that tricyclic antidepressants are
more effective than SSRIs but the evidence is
inconclusive. Also, in some studies which were not
necessarily in older people, venlafaxine has also
been shown to be more effective than the SSRIs in
the management of moderately severe depression5.
Venlafaxine at doses above 200mg/day
is a recommended treatment option in the
management of refractory depression16. This
complies with NICE guidelines that venlafaxine
should be considered in those who have failed to
respond to two trials of antidepressants.
It is very important to be aware that older people
take longer to respond to antidepressant treatment
and as a consequence are at risk of being
prematurely considered non responsive. They may
have their antidepressant switched when they
geriatric medicine / midlife and beyond / february 2006
Postural hypotension
Lowering of blood pressure is one of the most
common cardiac effects of antidepressants in
the elderly. When severe, it can result in postural
hypotension. Postural hypotension is partly due
to the blockade of alpha-1 adrenergic receptors.
The risk of postural hypotension is increased in
those with left sided heart failure and in those on
antihypertensive or diuretic treatment17.
The following antidepressants are associated
with high to moderate risk of postural hypotension
tricyclics, monoamine oxidase inhibitors,
trazodone, and nefazodone16. Lofepramine does
not lower blood pressure as much as the other
tricyclics, and although the risk is less, postural
hypotension can occur during treatment with
other antidepressants including venlafaxine,
mirtazapine and the SSRIs18. Venlafaxine can also
increase blood pressure especially at doses above
200mg daily thus blood pressure measurement
is recommended at higher doses. Postural drop
64 Psychiatry
tends to occur early in the course of treatment
and since it is not dose dependent, unless a patient
is on a high dose, dose reduction is unlikely to
be of benefit6. Postural hypotension is associated
with increased risk of falls and fractures. The risk
can be significantly reduced by checking for a
history of postural drop and by measuring standing
and supine blood pressures before prescribing
antidepressants that are associated with this side
effect, especially tricyclics. Postural hypotension
can be managed by changing to a different class of
antidepressant or, if for clinical reasons this is not
possible, fludrocortisone and pressure stockings
can be used.
Risk of overdose
Psychiatry 65
Table 1.
Antidepressants
Starting dose
Elderly
Maximum dose
Starting dose
Adults
Maximum dose
Dosulepin
Trazodone
Citalopram
Fluoxetine
50-75mg
100mg
20mg
20mg
75mg*
300mg
40mg
60mg
75mg
150mg
20mg
20mg
150mg
300mg
60mg
80mg
* (may be sufficient)
Delirium
Delirium and confusion can be induced by
antidepressant treatment. These are mainly due to
the anticholinergic and antihistaminic effects of the
antidepressant agent hence these particular side
effects are more likely to occur in those elderly
patients taking tricyclics rather than other groups
of antidepressants. The risk is greatest in those
with an underlying dementia. Delirium can present
with affective symptoms and because of this, may
be confused with worsening of depression. It is
very important to bear this possibility in mind
especially in those patients whose depression is
worsening despite adequate treatment.
Sexual dysfunction
Sexual dysfunction such as arousal problems,
reduced libido, delayed orgasm and impaired
ejaculation are recognised side effects associated
with all classes of antidepressants. Some
antidepressants are considered to be less
likely to cause sexual dysfunction. There
is however insufficient evidence in the literature
to support this claim. One systematic review
february 2006 / midlife and beyond / geriatric medicine
66 Psychiatry
found that available evidence was insufficient to
justify claims of differences in the propensities
of antidepressants to cause sexual dysfunction26.
Sexual side effects are often not reported but it
is necessary to consider them when discussing
the risk and benefit of a particular antidepressant.
Trazodone, for example, can rarely cause
priapism.
Akathisia
Akathisia is an extrapyramidal side effect that is
most often associated with typical antipsychotic
medications but can also be caused by
antidepressants. It is characterised by difficulty
staying still and an intense feeling of inner
restlessness. There is some evidence in support of
the view that akathisia induces suicidal behaviour27.
Bearing this in mind, clinicians are advised by
NICE to actively seek out signs of akathisia
especially in the early stages of treatment.
Akathisia can be difficult to diagnose, hence
a high index of suspicion is needed. It is managed
by withdrawing the offending drug or by reducing
the dose if this is possible. Where dose reduction is
not possible, the patient can be treated with a betablocker such propranolol and if this is ineffective
then a benzodiazepine such as diazepam or
clonazepam could be used28.
Dementia
A recent Cochrane review revealed that this
is a poorly researched area and as such there
is not much evidence supporting the efficacy
of antidepressants in people with dementia29.
geriatric medicine / midlife and beyond / february 2006
Parkinsons disease
Parkinsons disease is a disease of later life, and
40 to 50 per cent of people with Parkinsons
disease will experience co-morbid depression30.
The treatment of Parkinsons disease involves
the use of combinations of drugs with potential
risk of drug interaction. Therefore, prescribing an
antidepressant for co-morbid depression could
further increase this risk. Tricyclics and SSRIs
are effective pharmacotherapy for depression in
Parkinsons disease but there are some concerns
related to side effects. Tricyclics, for instance,
may worsen cognitive function, cause orthostatic
hypotension or induce delusions30.
There is also debate that SSRIs may worsen
parkinsonism. On the positive side, tricyclics
might help extrapyramidal symptoms due to their
anticholinergic effects31. Given their favourable
side effect profiles and reduced drug interactions,
SSRIs are recommended, particularly those with
neutral or weak dopaminergic effects such as
sertraline and citalopram. SSRIs should not be
prescribed for patients on selegiline (a monoamine
oxidase-B inhibitor) because of increased risk of
serotonin syndrome18.
Dose reduction
Despite the advancement in psychopharmacology,
the adage start low and go slow is advocated
when prescribing antidepressants in elderly people.
In working age adults, most new antidepressants
can be started at their therapeutic dose without
the need for dose titration. In the elderly dose
titration is often done in an effort to reduce
the risk of side effects. When dose titration is
carried out, it is important that the therapeutic
dose is achieved where tolerable although there
are studies suggesting that elderly people may
respond to lower doses of antidepressant. For
some antidepressants, the manufacturers have
Psychiatry 67
Key points
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Discontinuation syndrome
Discontinuation syndrome may occur following
abrupt cessation of antidepressant treatment.
Patients often report dizziness, nausea, vomiting,
flu like symptoms, fatigue, anxiety and irritability.
These symptoms are usually self limiting but on
occasions can be severe. All patients prescribed
antidepressants must be informed of the risk of
discontinuation syndrome9.
Discontinuation syndrome is more likely
with antidepressants with short half lives, such
as paroxetine. Fluoxetine, an antidepressant with
a long half life, is recommended as a means of
managing withdrawal symptoms in those patients
who have had difficulty in stopping treatment.
Also, when an antidepressant is to be stopped, this
should be done by gradual dose reduction over a
number of weeks.
Conclusion
SSRIs are currently the drugs of first choice in
the treatment of moderate to severe depression in
the elderly because of their more favourable side
effect profiles and lower risk of drug interaction.
However, it is important to select antidepressants
depending on the individual patient symptoms
and characteristics.
As a general rule, polypharmacy should be
avoided and older people may need more frequent
monitoring and slower dose titration than their
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